HIV-specific T-cells accumulate in the liver in HCV/HIV co-infection.
OBJECTIVE
Hepatitis C Virus (HCV)-related liver disease progresses more rapidly in individuals co-infected with Human Immunodeficiency Virus-1 (HIV), although the underlying immunologic mechanisms are unknown. We examined whether HIV-specific T-cells are identified in the liver of HCV/HIV co-infected individuals and promote liver inflammation through bystander immune responses.


METHODS
Ex-vivo intra-hepatic lymphocytes from HCV mono-infected and HCV/HIV co-infected individuals were assessed for immune responses to HIV and HCV antigens by polychromatic flow cytometry.


RESULTS
HCV/HIV liver biopsies had similar frequencies of lymphocytes but lower percentages of CD4+ T-cells compared to HCV biopsies. In co-infection, intra-hepatic HIV-specific CD8+ and CD4+ T-cells producing IFN-gamma and TNF-alpha were detected and were comparable in frequency to those that were HCV-specific. In co-infected individuals, viral-specific CD8+ T-cells produced more of the fibrogenic cytokine, TNF-alpha. In both mono- and co-infected individuals, intra-hepatic HCV-specific T-cells were poorly functional compared to HIV-specific T-cells. In co-infection, HAART was not associated with a reconstitution of intra-hepatic CD4+ T-cells and was associated with reduction in both HIV and HCV-specific intra-hepatic cytokine responses.


CONCLUSIONS
The accumulation of functional HIV-specific T-cells in the liver during HCV/HIV co-infection may represent a bystander role for HIV in inducing faster progression of liver disease.
Vali
Bahareh
B
Institute of Medical Science, Department of Medicine, University of Toronto, Toronto, Canada. bahareh.vali@utoronto.ca
Yue
Feng Yun
FY
Jones
R Brad
RB
Sheth
Prameet M
PM
Kaul
Rupert
R
Betts
Michael R
MR
Wong
David
D
Kovacs
Colin
C
Loutfy
Mona
M
Common
Andrew
A
Halpenny
Roberta
R
Ostrowski
Mario A
MA
D000956:Antigens, Viral / Q000032:analysis; D024201:Bystander Effect / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D016207:Cytokines / Q000032:analysis; D015658:HIV Infections / Q000150:complications*; D015497:HIV-1 / Q000276:immunology*; D006526:Hepatitis C / Q000150:complications*; D008099:Liver / Q000276:immunology* / Q000821:virology; D008107:Liver Diseases / Q000209:etiology / Q000276:immunology / Q000821:virology*; D037182:T-Cell Antigen Receptor Specificity; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology*
D000956:Antigens, Viral; D016207:Cytokines